The major thrust of this research proposal is the continuation of our work on various aspects of shock and hypoxia which are of particular importance for the surgical patient. Our previous observations of changes in cellular and subcellular function with shock and hypoxia will serve as the base on which we plan now to define, a) mechanisms and bases for such changes, b) the interrelationships and perhaps interdependency of such changes particularly of energy metabolism and transport phenomena, c) further areas of potential cellular malfunction, d) better definition of which cell populations in an organ may produce problems, i.e., parenchymal cells, microcirculation, endothelium, and e) therapeutic considerations aimed primarily at improving cell function. Specific areas of activity include, 1) further study of insulin resistance with shock which may serve as a model for membrane change. 2) study of energy metabolism including the kinetics of adenine nucleotide production with shock and its relationship to transport activity, 3) attempts to determine critical energy levels for various aspects of cell function, 4) study of ATP-MgCl2 administration -- where it goes and what it does, 5) NAD, cyclic AMP and the prostaglandins with shock, 6) study of specific types of cells within an organ which are altered by shock and vascular smooth muscle change, and 7) relationships of organ, ischemia, i.e., heart and kidney, to energy levels and ATP-MgCl2 administration.